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Meta-Analysis
. 2014 Jul 31;2014(7):CD009583.
doi: 10.1002/14651858.CD009583.pub2.

Nalbuphine for postoperative pain treatment in children

Alexander Schnabel  1 , Sylvia U Reichl, Peter K Zahn, Esther Pogatzki-Zahn
Affiliations
Meta-Analysis

Nalbuphine for postoperative pain treatment in children

Alexander Schnabel et al. Cochrane Database Syst Rev. .

Abstract

Background: Several surveys over the past few years have demonstrated that postoperative pain in children is not treated appropriately. One pharmacological treatment option in a multimodal approach for postoperative pain treatment is the systemic administration of opioids. However, opioids are rarely used for postoperative pain treatment in children due to fear of adverse events. One long-standing opioid for systemic use is nalbuphine, a kappa-receptor agonist and µ-receptor antagonist. The efficacy of nalbuphine is believed to be similar to morphine. Increased dosing might result in a ceiling effect, and thus less analgesia than expected. In addition, there might be a lower risk for opioid-induced side effects (nausea, vomiting) and severe adverse events (respiratory depression) due to the antagonistic effect of the µ-receptor. Nalbuphine may be an useful opioid for postoperative use in children, but exact efficacy (e.g. compared to other commonly used opioids) has not been determined yet.

Objectives: To assess the efficacy and adverse events of nalbuphine for acute postoperative pain treatment in children undergoing surgery.

Search methods: We systematically searched the following databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7), MEDLINE via Pubmed (January 1966 to July 2013) and EMBASE via Ovid (January 1947 to July 2013). We did not impose any restrictions regarding language or publication date. We checked all reference lists of retrieved articles for additional references.

Selection criteria: All randomised controlled trials (RCTs) investigating nalbuphine compared with placebo or other opioids were included.

Data collection and analysis: Two review authors independently scanned the retrieved articles and made a decision regarding inclusion or exclusion of studies for this review. The same authors also performed the data extraction and the assessment of risk of bias.

Main results: Ten RCTs including 658 patients were finally included in this systematic review. Five trials compared nalbuphine with placebo. Data from one out of five studies for the outcome moderate/severe pain following nalbuphine compared to placebo gave a risk ratio (RR) 1 hour postoperatively (postop) of 0.1 (95% confidence interval (CI) 0.01 to 0.71; low quality evidence) and a RR 2 hours postop of 0.14 (95% CI 0.02 to 1.06; low quality evidence). The estimated RR based on data from a single study indicated that nalbuphine reduced the requirement for analgesia two hours postop (RR 0.47; 95% CI 0.27 to 0.84; low quality evidence). Two included trials compared nalbuphine with morphine and showed a nonsignificant lower or comparable RR for moderate/severe pain at 1 hour postop (RR 0.84; 95% CI 0.12 to 5.74; low quality evidence), and 2 hours postop (RR 1.09; 95% CI 0.59 to 2.01; low quality evidence) for nalbuphine versus morphine. Four trials compared nalbuphine with tramadol for postoperative pain; data from one trial (per outcome) revealed a lower but nonsignificant RR for the need of additional rescue analgesics in children receiving nalbuphine (RR 2 hours postop 0.75; 95% CI 0.39 to 1.43; low quality evidence) (RR 12 hours postop 0.33; 95% CI 0.04 to 2.77; low quality evidence). One out of three trials comparing nalbuphine with pethidine demonstrated that the RR was not significantly lower following nalbuphine administration compared to pethidine (RR 2 hours postop 1.07; 95% CI 0.52 to 2.23; low quality evidence) (RR 24 hours postop 1.13; 95% CI 0.52 to 2.44; very low quality evidence). The most common adverse event was postoperative nausea and vomiting (PONV). Only one included trial reported that the RR for PONV in the postoperative care unit (PACU) was not significantly higher following nalbuphine compared to placebo (RR 1.00; 95% CI 0.16 to 6.42; low quality evidence) nor to morphine (RR 1.33; 95% CI 0.64 to 2.77; low quality evidence).

Authors' conclusions: Because the overall quality of available evidence was low, this systematic review could not definitively show that the analgesic efficacy of nalbuphine is superior compared to placebo. Furthermore, due to the lack of significant results the comparison with other common opioids is also unclear. The same holds true for the evidence focusing on adverse events following nalbuphine compared to placebo or other opioid administration. The evidence is limited, because studies did not report conclusively all important postoperative pain outcomes (e.g. number of patients with the need for rescue analgesia, postoperative pain scores). Thus, a quantitative analysis was not possible for many major aspects (e.g. rescue analgesia, pain scores) and heterogeneity could not be further explored.

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Conflict of interest statement

Alexander Schnabel: No conflicts of interest.

Sylvia Reichl: No conflicts of interest.

Peter Zahn: No conflicts of interest.

Esther Pogatzki‐Zahn: No conflicts of interest.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 1 Number of patients with moderate/severe pain (1h postop).
1.2
1.2. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 2 Number of patients with moderate/severe pain (2h postop).
1.3
1.3. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 3 Number of patients with the need for rescue analgesia (2h postop).
1.4
1.4. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 4 Number of patients with the need for rescue analgesia (12h postop).
1.5
1.5. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 5 Number of patients with PONV (PACU).
1.6
1.6. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 6 Number of patients with PONV (postop 24h).
1.7
1.7. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 7 Number of patient with vomiting (PACU).
1.8
1.8. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 8 Number of patients with vomiting (postop 24h).
1.9
1.9. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 9 Number of patients with pruritus (postop 24h).
1.10
1.10. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 10 Number of patients with respiratory depression.
1.11
1.11. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 11 Number of patients with urinary retention.
1.12
1.12. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 12 Number of patients with sedation (24h postop) ).
1.13
1.13. Analysis
Comparison 1 Nalbuphine versus placebo, Outcome 13 Number with patients with bradycardia (PACU).
2.1
2.1. Analysis
Comparison 2 Nalbuphine versus morphine, Outcome 1 Number of patients with moderate/severe pain (1h postop).
2.2
2.2. Analysis
Comparison 2 Nalbuphine versus morphine, Outcome 2 Number of patients with moderate/severe pain (2h postop).
2.3
2.3. Analysis
Comparison 2 Nalbuphine versus morphine, Outcome 3 Number of patients with the need for rescue analgesia (12h postop).
2.4
2.4. Analysis
Comparison 2 Nalbuphine versus morphine, Outcome 4 Number of patients with PONV (PACU).
2.5
2.5. Analysis
Comparison 2 Nalbuphine versus morphine, Outcome 5 Number of patients with PONV (24h postop).
2.6
2.6. Analysis
Comparison 2 Nalbuphine versus morphine, Outcome 6 Number of patient with respiratory depression.
2.7
2.7. Analysis
Comparison 2 Nalbuphine versus morphine, Outcome 7 Number with patient with bradycardia (PACU).
3.1
3.1. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 1 Number of patients with moderate/severe pain (1h postop).
3.2
3.2. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 2 Number of patients with the need for rescue analgesia (2h postop).
3.3
3.3. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 3 Number of patients with the need for rescue analgesia (12h postop).
3.4
3.4. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 4 Number of patients with the need for rescue analgesia (24h postop).
3.5
3.5. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 5 Number of patients with PONV (24h postop).
3.6
3.6. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 6 Number of patients with vomiting (PACU).
3.7
3.7. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 7 Number of patients with vomiting (24h postop).
3.8
3.8. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 8 Number of patients with respiratory depression (PACU).
3.9
3.9. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 9 Number of patients with sedation (24h postop).
3.10
3.10. Analysis
Comparison 3 Nalbuphine versus tramadol, Outcome 10 Number of patients with bradycardia (PACU).
4.1
4.1. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 1 Number of patients with moderate/severe pain (1h postop).
4.2
4.2. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 2 Number of patients with the need for rescue analgesia (2h postop).
4.3
4.3. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 3 Number of patients with the need for rescue analgesia (24h postop).
4.4
4.4. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 4 Time to first rescue analgesic (h).
4.5
4.5. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 5 Number of patients with vomiting (PACU).
4.6
4.6. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 6 Number of patients with vomiting (24h postop).
4.7
4.7. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 7 Number of patients with respiratory depression (PACU).
4.8
4.8. Analysis
Comparison 4 Nalbuphine versus pethidine, Outcome 8 Number of patients with bradycardia (PACU).
5.1
5.1. Analysis
Comparison 5 Nalbuphine versus piritramid, Outcome 1 Number of patients with the need for rescue analgesia (24h postop).
5.2
5.2. Analysis
Comparison 5 Nalbuphine versus piritramid, Outcome 2 Number of patients with PONV (24h postop).
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Update of

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